https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Brian+OchoaProteopedia - User contributions [en]2026-09-19T18:45:49ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=RING_Finger_Domain_of_BRCA1_and_BARD1_Heterodimer&diff=2588789RING Finger Domain of BRCA1 and BARD1 Heterodimer2016-04-28T03:54:08Z<p>Brian Ochoa: </p>
<hr />
<div><Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='[[1jm7]]' /><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a RING finger motif from position 24 to 64. The RING motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The RING motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the RING motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the RING motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the RING motif. These alpha helices from the RING motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
<br />
== Functional Highlights ==<br />
One main function of the RING finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain RING finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residues using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. The positioning is proposed to be facilitated through an interaction of the RING domain with a hydrophobic region of the donor ubiquitin. The correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site contributed by the E2 have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of the RING finger's ability to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=RING_Finger_Domain_of_BRCA1_and_BARD1_Heterodimer&diff=2588784RING Finger Domain of BRCA1 and BARD1 Heterodimer2016-04-28T03:50:32Z<p>Brian Ochoa: </p>
<hr />
<div><Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='[[1jm7]]' /><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a RING finger motif from position 24 to 64. The RING motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The RING motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the RING motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the RING motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the RING motif. These alpha helices from the RING motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
<br />
== Functional Highlights ==<br />
One main function of the RING finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain RING finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residues using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. The positioning is proposed to be facilitated through an interaction of the RING domain with a hydrophobic region of the donor ubiquitin. The correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site contributed by the E2 have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=RING_Finger_Domain_of_BRCA1_and_BARD1_Heterodimer&diff=2588595RING Finger Domain of BRCA1 and BARD1 Heterodimer2016-04-27T13:16:45Z<p>Brian Ochoa: </p>
<hr />
<div><Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='[[1jm7]]' /><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a RING finger motif from position 24 to 64. The RING motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The RING motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the RING motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the RING motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the RING motif. These alpha helices from the RING motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
<br />
== Functional Highlights ==<br />
One main function of the RING finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain RING finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residues using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. The positioning is proposed to be facilitated through an interaction of the RING domain with a hydrophobic region of the donor ubiquitin. Th correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site contributed by the E2 have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=RING_Finger_Domain_of_BRCA1_and_BARD1_Heterodimer&diff=2588527RING Finger Domain of BRCA1 and BARD1 Heterodimer2016-04-26T22:58:38Z<p>Brian Ochoa: </p>
<hr />
<div><Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a RING finger motif from position 24 to 64. The RING motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The RING motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the RING motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the RING motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the RING motif. These alpha helices from the RING motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
<br />
== Functional Highlights ==<br />
One main function of the RING finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain RING finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residues using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. Correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=RING_Finger_Domain_of_BRCA1_and_BARD1_Heterodimer&diff=2588522RING Finger Domain of BRCA1 and BARD1 Heterodimer2016-04-26T22:43:05Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. Correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=RING_Finger_Domain_of_BRCA1_and_BARD1_Heterodimer&diff=2588521RING Finger Domain of BRCA1 and BARD1 Heterodimer2016-04-26T22:42:32Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. Correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=RING_Finger_Domain_of_BRCA1_and_BARD1_Heterodimer&diff=2588520RING Finger Domain of BRCA1 and BARD1 Heterodimer2016-04-26T22:41:46Z<p>Brian Ochoa: New page: ==Your Heading Here (maybe something like 'Structure')== ==1jm7== <Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /> This is a default text for...</p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. Correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588519User:Brian Ochoa/Sandbox 12016-04-26T22:38:29Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
As highlighted by Dr. Berndsen in his review, the mechanism by which the RING domain facilitates the transfer of the ubiquitin from the E2 to the target protein is largely by allosteric means. The heterodimer of BRCA1-BARD1 is believed to position the donor ubiquitin on the E2 protein in the active site so that the thioester bond between the E2 and the C-terminus of the donor ubiquitin can be easily attacked by the lysine. Correct positioning of this bond by the RING domain thus helps increase the reaction rate of hydrolysis of the thioester. Other conserved residues in the active site have been proposed to facilitate ubiquitination such as acidic residues which may deprotonate, and thus activate the attacking lysine. Additionally, a conserved asparagine has been suggested to be important to either stabilize the oxyanion intermediate or maintain the correct orientation of active site residues. <ref>Berndsen, C. E.; Wolberger, C. New Insights into Ubiquitin E3 Ligase Mechanism. Nat Struct Mol Biol Nature Structural & Molecular Biology. 2014, 21, 301–307.</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588518User:Brian Ochoa/Sandbox 12016-04-26T22:28:15Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588515User:Brian Ochoa/Sandbox 12016-04-26T22:23:40Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1_3/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588509User:Brian Ochoa/Sandbox 12016-04-26T22:19:06Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1_2/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588503User:Brian Ochoa/Sandbox 12016-04-26T22:13:19Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1_2/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588486User:Brian Ochoa/Sandbox 12016-04-26T21:08:02Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588485User:Brian Ochoa/Sandbox 12016-04-26T21:07:38Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a <scene name='72/727979/Practice/1'>C3HC4 zinc-binding motif scene</scene>, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588452User:Brian Ochoa/Sandbox 12016-04-26T14:32:27Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<scene name='72/727979/Practice/1'>practice scene</scene><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1/1'>BRCA1</scene> forms a heterodimer with the ring motif of <scene name='72/727979/Bard1/1'>BARD1</scene> to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588450User:Brian Ochoa/Sandbox 12016-04-26T14:27:44Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<scene name='72/727979/Practice/1'>practice scene</scene><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of <scene name='72/727979/Brca1/1'>BRCA1</scene> forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588446User:Brian Ochoa/Sandbox 12016-04-26T14:07:23Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<scene name='72/727979/Practice/1'>practice scene</scene><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a <scene name='72/727979/Practice_2/1'>four-helix bundle</scene> that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2588409User:Brian Ochoa/Sandbox 12016-04-26T01:14:05Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<scene name='72/727979/Practice/1'>practice scene</scene><br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586826User:Brian Ochoa/Sandbox 12016-04-12T23:26:27Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='1jm7' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586825User:Brian Ochoa/Sandbox 12016-04-12T23:26:07Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='''1jm7''' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586823User:Brian Ochoa/Sandbox 12016-04-12T23:25:01Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='BRCA1 Gene' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586822User:Brian Ochoa/Sandbox 12016-04-12T23:24:38Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<Structure load='1jm7' size='300' color='black' frame='true' align='right' caption='BRCA1 Gene' /><br />
<br />
<br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle.<ref>Ruffner, H., Joazeiro, C. A., Hemmati, D., Hunter, T., & Verma, I. M. (2001, April 24). Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Retrieved April 12, 2016, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/<br />
doi: 10.1073/pnas.081068398</ref> A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586820User:Brian Ochoa/Sandbox 12016-04-12T23:06:06Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA sequence shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression, Used to gather information about the BRCA1 </ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue. <ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/]. A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586819User:Brian Ochoa/Sandbox 12016-04-12T22:56:50Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
<br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA Seq shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression<br />
Used to gather information about the BRCA1 location.</ref>Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/]. A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586818User:Brian Ochoa/Sandbox 12016-04-12T22:46:49Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA Seq shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression<br />
Used to gather information about the BRCA1 location.</ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Medical Significance ==<br />
Mutations in BRCA1 are responsible for a large amount of breast and ovarian cancers. Inherited mutations in the RING finger, exons 11-13, and the BRCT domain, along with loss of heterozygosity, are the most common mutations that lead to breast or ovarian cancer.<ref>Clark, S. L., Rodriguez, A. M., Snyder, R. R., Hankins, G. D., & Boehning, D. (n.d.). Structure-Function of the Tumor Suppressor BRCA1. Retrieved April 12, 2016, from https://www.researchgate.net/publication/228072103_Structure-Function_of_the_Tumor_Suppressor_BRCA1<br />
doi:10.5936/csbj.201204005</ref> Specifically, many RING finger E3s play a vital role in maintaining genomic integrity and homeostasis, and as a result are implicated either in the suppression or progression in cancer.<ref>Lipkowitz, S., & Weissman, A. M. (2011). RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nature Reviews Cancer Nat Rev Cancer, 11(9), 629-643. doi:10.1038/nrc3120</ref> These mutants are also unable to reverse γ-radiation hypersensitivity in addition to becoming incapable of restoring the G2 + M checkpoint in the cell cycle [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC33176/]. A mutation here could result in partial or complete loss of ability of the RING finger to suppress cancerous growths. A frameshift mutation in ovarian epithelial cell lines has also been found to interrupt RING domain function, which ultimately altered caspase 3 activation and lead to staurosporine induced apoptosis.<ref>Johnson, N. C., & Kruk, P. A. (2002, July 2). Cancer Cell International. Retrieved April 12, 2016, from http://cancerci.biomedcentral.com/articles/10.1186/1475-2867-2-7<br />
DOI: 10.1186/1475-2867-2-7</ref><br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586817User:Brian Ochoa/Sandbox 12016-04-12T22:36:31Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Location Summary ==<br />
<br />
RNA Seq shows that BRCA1 is commonly expressed in many tissue types.<ref>GeneCards: Human Gene Database. (n.d.). Retrieved April 12, 2016, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1#expression<br />
Used to gather information about the BRCA1 location.</ref> Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref> On a subcellular level, BRCA1 is distributed throughout the nucleoplasm in resting and G1 cycling cells. Once the cells prepare to replicate, BRCA1 accumulates into nuclear bodies that also contain BARD1 and other DNA repair proteins. These nuclear bodies act as emergency response teams, ready to be sent to sites of DNA damage.<ref>Mutations resulting in tumor growth, however, are primarily seen in breast and ovarian tissue.<ref>Location of BRCA1 in Human Breast and Ovarian Cancer Cells. (n.d.). Retrieved April 12, 2016, from http://science.sciencemag.org/content/272/5258/123<br />
DOI: 10.1126/science.272.5258.123</ref><br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586816User:Brian Ochoa/Sandbox 12016-04-12T22:26:31Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref><br />
== Functional Highlights ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit.<ref>Clapperton, J. A., Manke, I. A., Lowery, D. M., Ho, T., Haire, L. F., Yaffe, M. B., & Smerdon, S. J. (2004). Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol Nature Structural & Molecular Biology, 11(6), 512-518. doi:10.1038/nsmb775</ref> Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals.<ref> Morris, J. R. (2004). BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Human Molecular Genetics, 13(8), 807-817. doi:10.1093/hmg/ddh095<br />
</ref> <br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586815User:Brian Ochoa/Sandbox 12016-04-12T22:18:17Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Function ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions.<ref>Borden, K. L., & Freemont, P. S. (n.d.). The RING finger domain: A recent example of a sequence—structure family. Retrieved April 12, 2016, from http://www.sciencedirect.com/science/article/pii/S0959440X96800601<br />
doi:10.1016/S0959-440X(96)80060-1</ref> Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another (http://www.jbc.org/content/274/9/5659.full).<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586814User:Brian Ochoa/Sandbox 12016-04-12T22:11:42Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Function ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region. <ref>Meza, J. E., Brzovic, P. S., King, M., & Kelvin, R. E. (n.d.). Mapping the Functional Domains of BRCA1. Retrieved April 12, 2016, from http://www.jbc.org/content/274/9/5659.full#fn-5<br />
doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions (http://www.sciencedirect.com/science/article/pii/S0959440X96800601). Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another (http://www.jbc.org/content/274/9/5659.full).<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User_talk:Brian_Ochoa/Sandbox_1&diff=2586813User talk:Brian Ochoa/Sandbox 12016-04-12T21:51:25Z<p>Brian Ochoa: </p>
<hr />
<div>==Ring Finger Domain of BRCA1==<br />
<StructureSection load='1jm7' size='340' side='right' caption='1jm7' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region.<ref>doi: 10.1074/jbc.274.9.5659</ref> The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions. Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <br />
== Function ==<br />
One main function of the ring finger domain of BRCA1 is to mediate heterodimer formation with BARD1. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Another main function is to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome. BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit. Ubiquination of lysine-63 controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals. <br />
<br />
<br />
== Disease ==<br />
<br />
<br />
== Relevance ==<br />
<br />
==Critical Amino Acids==<br />
<br />
==Abbreviations== <br />
<br />
BCRA1-breast cancer gene 1; BARD-BRCA1 associated ring domain;<ref>DOIakljsdfajldfjahdflkjasdfhasdhfjklahdflhalskjdfhakljsdfhl</ref> <br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User_talk:Brian_Ochoa/Sandbox_1&diff=2586811User talk:Brian Ochoa/Sandbox 12016-04-12T21:45:34Z<p>Brian Ochoa: </p>
<hr />
<div>==Ring Finger Domain of BRCA1==<br />
<StructureSection load='1jm7' size='340' side='right' caption='1jm7' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region. The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions. Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <br />
== Function ==<br />
The two main functions of the ring finger domain of BRCA1 are to mediate heterodimer formation with BARD1 and to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome. Ubiquination of lysine-63 on the over hand, controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals. <br />
<br />
== Disease ==<br />
<br />
<br />
== Relevance ==<br />
<br />
==Critical Amino Acids==<br />
<br />
==Abbreviations== <br />
<br />
BCRA1-breast cancer gene 1; BARD-BRCA1 associated ring domain;<ref>DOIakljsdfajldfjahdflkjasdfhasdhfjklahdflhalskjdfhakljsdfhl</ref> <br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User_talk:Brian_Ochoa/Sandbox_1&diff=2586810User talk:Brian Ochoa/Sandbox 12016-04-12T21:44:13Z<p>Brian Ochoa: </p>
<hr />
<div>==Ring Finger Domain of BRCA1==<br />
<StructureSection load='1jm7' size='340' side='right' caption='1jm7' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region. The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions. Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <br />
== Function ==<br />
The two main functions of the ring finger domain of BRCA1 are to mediate heterodimer formation with BARD1 and to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome. Ubiquination of lysine-63 on the over hand, controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals. <br />
<br />
== Disease ==<br />
<br />
<br />
== Relevance ==<br />
<br />
==Critical Amino Acids==<br />
<br />
==Abbreviations== <br />
<br />
<ref>BCRA1-breast cancer gene 1; BARD-BRCA1 associated ring domain;</ref> <br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User_talk:Brian_Ochoa/Sandbox_1&diff=2586808User talk:Brian Ochoa/Sandbox 12016-04-12T21:30:53Z<p>Brian Ochoa: </p>
<hr />
<div>==Ring Finger Domain of BRCA1==<br />
<StructureSection load='1jm7' size='340' side='right' caption='1jm7' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region. The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions. Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <br />
== Function ==<br />
The two main functions of the ring finger domain of BRCA1 are to mediate heterodimer formation with BARD1 and to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome. Ubiquination of lysine-63 on the over hand, controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals. <br />
<br />
== Disease ==<br />
<br />
<br />
== Relevance ==<br />
<br />
==Critical Amino Acids==<br />
<br />
==Abbreviations== <br />
<br />
BCRA1-breast cancer gene 1; BARD-BRCA1 associated ring domain;<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User_talk:Brian_Ochoa/Sandbox_1&diff=2586807User talk:Brian Ochoa/Sandbox 12016-04-12T21:29:52Z<p>Brian Ochoa: </p>
<hr />
<div>==Ring Finger Domain of BRCA1==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region. The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions. Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <br />
== Function ==<br />
The two main functions of the ring finger domain of BRCA1 are to mediate heterodimer formation with BARD1 and to catalyze ubiquination of lysine residue using ubiquitin from E2 enzymes. BRCA1 also moves to areas within the cell containing damaged DNA and acts as scaffolding for repair complexes to sit. BARD1 and BRCA1 are able to form a heterodimer because they both contain ring finger domains that interact with each other. Ubiquination of lysine-48 is a means of marking a protein for degradation by the proteasome. Ubiquination of lysine-63 on the over hand, controls DNA repair pathways as well as activate protein kinases by sending out non-proteolytic signals. <br />
<br />
== Disease ==<br />
<br />
<br />
== Relevance ==<br />
<br />
==Critical Amino Acids==<br />
<br />
==Abbreviations== <br />
<br />
BCRA1-breast cancer gene 1; BARD-BRCA1 associated ring domain;<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User_talk:Brian_Ochoa/Sandbox_1&diff=2586806User talk:Brian Ochoa/Sandbox 12016-04-12T21:26:15Z<p>Brian Ochoa: </p>
<hr />
<div>==Ring Finger Domain of BRCA1==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Structural Highlights ==<br />
BRCA1 is an 1,863 amino acid long protein that contains a ring finger motif from position 24 to 64. The ring motif is part of a larger domain spanning the first one hundred amino acid residues, which is required for the formation of its stable structure. This N-terminus domain is of the most highly conserved region of the BRCA1 gene and several cancer-predisposition mutations have been identified in this region. The ring motif is also a C3HC4 zinc-binding motif, named so for the conserved pattern of cysteine and histidines residues that bind the zinc ions. Ultimately, the ring motif of BRCA1 forms a heterodimer with the ring motif of BARD1 to assemble the functional protein complex. The solution structure of this complex shows that long alpha helices border the zinc binding residues in the ring motif. These alpha helices from the ring motif’s of BRCA1 and BARD1 combine to form a four-helix bundle that stabilizes the heterodimer and positions the zinc binding regions next to one another. <br />
== Function ==<br />
<br />
<br />
== Disease ==<br />
<br />
<br />
== Relevance ==<br />
<br />
==Critical Amino Acids==<br />
<br />
==Abbreviations== <br />
<br />
BCRA1-breast cancer gene 1; BARD-BRCA1 associated ring domain;<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2586805User:Brian Ochoa/Sandbox 12016-04-12T21:12:59Z<p>Brian Ochoa: </p>
<hr />
<div>==1jm7==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585757User:Brian Ochoa/Sandbox 12016-04-06T15:52:08Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<Structure load='1jm7' size='350' frame='true' align='right' caption='BRCA1 Gene' scene='Insert optional scene name here' /><br />
<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585756User:Brian Ochoa/Sandbox 12016-04-06T15:51:44Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<Structure load='1jm7' size='350' frame='true' align='right' caption='BRCA1 Gene' scene='Insert optional scene name here' /><br />
<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
Hi my name is Liss<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585666User:Brian Ochoa/Sandbox 12016-04-05T21:57:24Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
<br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<Structure load='1jm7' size='350' frame='true' align='right' caption='BRCA1 Gene' scene='Insert optional scene name here' /><br />
<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585665User:Brian Ochoa/Sandbox 12016-04-05T21:56:14Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<Structure load='1jm7' size='350' frame='true' align='right' caption='BRCA1 Gene' scene='Insert optional scene name here' /><br />
<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585664User:Brian Ochoa/Sandbox 12016-04-05T21:54:36Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
<Structure load='1m7' size='350' frame='true' align='right' caption='BRCA1 Gene'Insert optional scene name here' /><br />
<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585663User:Brian Ochoa/Sandbox 12016-04-05T21:48:41Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
[[ligand]]<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585662User:Brian Ochoa/Sandbox 12016-04-05T21:33:08Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7a' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585661User:Brian Ochoa/Sandbox 12016-04-05T21:30:12Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585660User:Brian Ochoa/Sandbox 12016-04-05T21:20:11Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='2otx' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
<table><tr><td colspan='2'>[[3w1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1M FirstGlance].<br />
== Disease ==<br />
<scene name='72/727979/Test_1/1'>TextToBeDisplayed</scene><br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585659User:Brian Ochoa/Sandbox 12016-04-05T21:16:02Z<p>Brian Ochoa: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='2otx' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
<br />
== Function ==<br />
Ciiii<br />
== Disease ==<br />
<scene name='72/727979/Test_1/1'>TextToBeDisplayed</scene><br />
== Relevance ==<br />
<br />
== Structural highlights ==<br />
<br />
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
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</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa/Sandbox_1&diff=2585264User:Brian Ochoa/Sandbox 12016-03-31T21:52:42Z<p>Brian Ochoa: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...</p>
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<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
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== Function ==<br />
Ciiii<br />
== Disease ==<br />
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== Relevance ==<br />
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== Structural highlights ==<br />
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
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</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User_talk:Brian_Ochoa/Sandbox_1&diff=2585263User talk:Brian Ochoa/Sandbox 12016-03-31T21:47:06Z<p>Brian Ochoa: </p>
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<div>==Your Heading Here (maybe something like 'Structure')==<br />
<StructureSection load='1jm7' size='340' side='right' caption='Caption for this structure' scene=''><br />
This is a default text for your page '''Brian Ochoa/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br />
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br />
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== Function ==<br />
HIIIIIII<br />
== Disease ==<br />
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== Relevance ==<br />
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==Critical Amino Acids==<br />
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==Abbreviations== <br />
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BCRA1-breast cancer gene 1; BARD-BRCA1 associated ring domain;<br />
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== Structural highlights ==<br />
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br />
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</StructureSection><br />
== References ==<br />
<references/></div>Brian Ochoahttps://proteopedia.org/index.php?title=User:Brian_Ochoa&diff=2585261User:Brian Ochoa2016-03-31T21:36:37Z<p>Brian Ochoa: </p>
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<div>* Full Real Name: Brian Ochoa<br />
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* Position: Student<br />
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* Institution (NO ABBREVIATIONS): James Madison University <br />
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* City, State/Province, Country: McLean, VA, U.S.A<br />
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* Field of Expertise or Study: Biology<br />
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*[[User:Brian Ochoa/Sandbox 1]]</div>Brian Ochoahttps://proteopedia.org/index.php?title=Elizeu/sandbox/citocromo_c&diff=2585260Elizeu/sandbox/citocromo c2016-03-31T21:26:39Z<p>Brian Ochoa: </p>
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<div><Structure load='1chc' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /><Structure load='4riu' size='350' frame='true' align='right' caption='4RIU' scene='Insert optional scene name here' /><br />
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==Description/Function==<br />
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The Ring finger motif of BRCA1 is located near the N-terminus (residues 24 - 64). The Ring finger motif does not form a stable structure by itself. Rather it is a part of larger domains comprising residues 1-109 of BRCA1. The first 100 residues, including the Ring finger motif, are the most highly conserved regions among known BRCA1 genes. It is also a zinc-binding motif, conserved pattern of cysteine and histidine residues<br />
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==Abbreviations==<br />
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RING-really interesting new gene; BRCA1- Breast Cancer 1 gene;<br />
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==Ligands==<br />
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E3 Ubiquitin Ligase <br />
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==Focal Points==<br />
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Many cancers are made exceedingly invasive when tumors are subjected to hypoxic stresses triggered by a decrease of oxygen in the tumor’s microenvironment or by aspects involved with inflammation. Hypoxic stress increases tumor growth, metastasis, invasiveness and resistance to treatments. When under hypoxic stress the pH of the tumor’s microenvironment decreases while the pH inside the tumor stays fairly normal and when this differential environment is altered it is fatal to the tumor cells. Carbonic anhydrase IX influences the differential pH and when it is inhibited it decreases tumor growth and enhances the effectiveness of cancer treatments. Saccharin binds to CA IX with nano molar affinity and preferential binding thus inhibiting CA IX.<br />
The SAC has a preference in binding to CA IX and CA XII over CA I and II. This is believed to be due to the substitution of PHE131 for Val in CA IX. It binds directly to the catalytic zinc of the CA IX-mimic displacing the zinc-bound OH-/H2O. <br />
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==Critical Amino Acids==<br />
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<scene name='55/559112/Leu_91/1'>Leu 91</scene><br />
<scene name='55/559112/Leu_198/1'>Leu 198</scene><br />
<scene name='55/559112/Val_131/2'>Val 131</scene><br />
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==References==<br />
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Brian P. Mahon, Alex M. Hendon, Jenna M. Driscoll, Gregory M. Rankin, Sally-Ann Poulsen, Claudiu T. Supuran, Robert McKenna, Saccharin: A lead compound for structure-based drug design of carbonic anhydrase IX inhibitors, Bioorganic & Medicinal Chemistry, Volume 23, Issue 4, 15 February 2015, Pages 849-854, ISSN 0968-0896, http://dx.doi.org/10.1016/j.bmc.2014.12.030.<br />
(http://www.sciencedirect.com/science/article/pii/S0968089614008785)<br />
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====Authors====<br />
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Elizabeth A. Dunlap, Preeti K. Deol</div>Brian Ochoa